The goal of this research is to understand the molecular and cellular basis underlying mammalian chemical communication using the mouse as a model system. To reach this goal, we will take advantage of a novel functional link between the immune system and the sense of smell by which information about the immunological genotype of an individual conspecific can be converted into a chemosensory quality. This mechanism is based on the detection of a large family of peptide ligands - the MHC class I peptides - by sensory neurons in the mammalian nose. Increasing evidence indicates that the highly polymorphic genes of the major histocompatibility complex (MHC) influence mating preference and other social behaviors in mice and humans. Detection of MHC peptides provides a molecular mechanism by which this can occur. This research has three specific aims. In aim 1, we will determine how these immune system signals are encoded in spatial patterns of neuronal activity in the vomeronasal organ (VNO) and whether specific receptors are involved in this process. In aim 2, we will investigate how immune system signals are encoded in specific temporal patterns of neural activity in the VNO. And in aim 3, we will determine how immune system signals are encoded by neuronal populations in the main olfactory epithelium. This research employs a highly interdisciplinary approach involving gene-targeting methodology, analysis of cellular activity using sophisticated electrophysiological and imaging methods, and behavioral analysis in wildtype and mutant mice. The relevance of this research lies in the fact that it provides a sensory mechanism by which an individual can detect the genetic composition and compatibility of the immune system of a conspecific, information that is likely to influence a variety of social behaviors. A potential application of this reseach is in the development of olfactory sensors that can identify an individual based on genetically-determined odors. [unreadable] [unreadable]